Vessel wall injury exposes tissue factor (TF) to the blood circulation and TF forms a complex with Factor VII/activated Factor VII (FVII/FVIIa) on the surface of TF-bearing cells. This leads to the activation of Factor X (FX) to FXa which together with FVa generates a limited amount of thrombin (FIIa). Small amounts of thrombin activate platelets, and this results in surface exposure of phospholipids that supports the binding of the tenase complex consisting of FVIIIa/FIXa
The tenase complex produces large amounts of FXa, which subsequently facilitates a full thrombin burst. A full thrombin burst is needed for the formation of a mechanically strong fibrin structure and stabilization of the haemostatic plug. FVIII or FIX is missing or present at low levels in haemophilia patients, and due to the lack of tenase activity, the capacity to generate FXa is low and insufficient to support the propagation phase of the coagulation. In contrast, the TF-mediated initiation phase is not dependent on the formation of the tenase complex. However, the TF-pathway will, shortly after an initial FXa generation, be blocked by plasma inhibitors.
Tissue factor pathway inhibitor (TFPI) downregulates ongoing coagulation by neutralizing the catalytic activity of FXa and by inhibition of the TF-FVIIa complex in the presence of FXa. TFPI either inhibits the TF/FVIIa/FXa complex on the cellular surface or inhibits released FXa followed by FVIIa/TF inhibition.